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Plant-derived polyphenols are naturally occurring compounds widely distributed in plants. They have received greater attention in the food and pharmaceutical industries due to their potential health benefits, reducing the risk of some chronic diseases due to their antioxidant, anti-inflammatory, anticancer, cardioprotective, and neuro-action properties. Polyphenolic compounds orally administered can be used as adjuvants in several treatments but with restricted uses due to chemical instability. The review discusses the different structural compositions of polyphenols and their influence on chemical stability. Despite the potential and wide applications, there is a need to improve the delivery of polyphenolics to target the human intestine without massive chemical modifications. Oral administration of polyphenols is unfeasible due to instability, low bioaccessibility, and limited bioavailability. Nano-delivery systems based on polysaccharides (starch, pectin, chitosan, and cellulose) have been identified as a viable option for oral ingestion, potentiate biological effects, and direct-controlled delivery in specific tissues. The time and dose can be individualized for specific diseases, such as intestinal cancer. This review will address the mechanisms by which polysaccharides-based nanostructured systems can protect against degradation and enhance intestinal permeation, oral bioavailability, and the potential application of polysaccharides as nanocarriers for the controlled and targeted delivery of polyphenolic compounds.

Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyphenols from pigmented cereal grains exert health-promoting effects but data on their bioavailability are limited. This study investigated the acute bioavailability of polyphenols from the consumption of pigmented whole grain cereal porridges, including purple barley (PB), purple wheat (PW), and blue wheat (BW), compared to a non-pigmented regular wheat (RW). A secondary objective was to assess their effects on plasma antioxidant and inflammatory status postprandially. Phenolic characterisation and antioxidant profiling were performed on extracts from the cooked cereals. Three healthy individuals consumed 200 g of a cereal in a 4-way crossover trial with a one-week washout in between meals. Blood samples were collected at fasting baseline, 30 minutes, 1 hour, 2 hours and 4 hours postprandially. Urine samples were collected at fasting baseline and the 4-hour time point. Pigmented grains exhibited significantly higher phenolic content and antioxidant capacity ( p < 0.001) compared to RW. This suggests that pigmented grains may be a better source of polyphenols and potentially offer greater health benefits. However, polyphenol bioavailability following pigmented grain consumption was reduced (less than 6%), suggesting that a substantial fraction remained unabsorbed. The bioavailable phenolic compounds detected included phenolic acids (protocatechuic and caffeic acid), hippuric acid and other phenolic metabolites. Interpersonal variability and the type of grain consumed had an impact on the absorption and excretion of phenolic acids. Only PW consumption resulted in significant ( p < 0.01) increases in plasma antioxidant status but no short-term impact on the inflammatory status. This study provides valuable insights into the complex dynamics of polyphenol bioavailability from pigmented cereal consumption and warrants further investigation.

Ethnopharmacological Relevance: Thymus quinquecostatus Celak., a member of thymus genus in Lamiaceae family, has been used as a folk medicine for relieving exterior syndrome and alleviating pain in China. The polyphenol-rich fraction (PRF) derived from Thymus quinquecostatus Celak. had been validated that it can protect cerebral ischemia-reperfusion injury (CIRI) by activating Keap1/Nrf2/HO-1 signaling pathway., Aim of This Study: To explore effective components and their pharmacokinetic and pharmacodynamic characteristics as well as possible mechanisms of PRF in treating CIRI., Materials and Methods: Normal treated group (NTG) and tMCAO model treated group (MTG) rats were administrated PRF intragastrically. The prototype components and metabolites of PRF in plasma and brain were analyzed by the UPLC-Q-Exactive Orbitrap MS n method. Subsequently, the pharmacokinetics properties of indicative components were performed based on HPLC-QQQ-MS/MS. SOD and LDH activities were determined to study the pharmacodynamic (PD) properties of PRF. The PK-PD relationship of PRF was constructed. In addition, the effect of PRF on endogenous metabolites in plasma and brain was investigated using metabolomic method., Results: Salvianic acid A, caffeic acid, rosmarinic acid, scutellarin, and apigenin-7-O-glucuronide were selected as indicative components based on metabolic analysis. The non-compartmental parameters were calculated for indicative components in plasma and brain of NTG and MTG rats. Furthermore, single-component and multi-component PK-PD modeling involved E max , I max PD models for effect indexes were fitted as well as ANN models were established, which indicated that these components can work together to regulate SOD and LDH activities in plasma and SOD activity in brain tissue to improve CIRI. Additionally, PRF may ameliorate CIRI by regulating the disorder of endogenous metabolites in lipid metabolism, amino acid metabolism, and purine metabolism pathways in vivo, among which lipid metabolism and purine metabolism are closely related to oxidative stress., Conclusion: The PK-PD properties of effect substances and mechanisms of PRF anti-CIRI were further elaborated. The findings provide a convincing foundation for the application of T. quinquecostatus Celak. in the maintenance of human health disorders., Competing Interests: Declaration of Competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this research, we utilized molecular simulations to create co-amorphous materials (CAMs) of ceritinib (CRT) with the objective of improving its solubility and bioavailability. We identified naringin (NRG) as a suitable co-former for CRT CAMs based on binding energy and intermolecular interactions through computational modeling. We used the solvent evaporation method to produce CAMs of CRT and NRG, expecting to enhance both solubility and bioavailability simultaneously. The solid-state characterization using techniques like differential scanning calorimeter, X-ray powder diffraction, and Fourier-transform infrared spectroscopy affirmed the formation of a single amorphous phase and the presence of intermolecular interactions between CRT and NRG in the CAMs. These materials remained physically stable for up to six months under dry conditions at 40 °C. Moreover, the CAMs demonstrated significant improvements in the solubility and dissolution of CRT (specifically in the ratio CRT:NRG 1:2). This, in turn, led to an increase in cytotoxicity, apoptotic cells, and G0/G1 phase inhibition in A549 cells compared to CRT alone. Furthermore, CRT permeability is also improved twofold, as estimated by the everted gut sac method. The enhanced solubility of CAMs also positively affected the pharmacokinetic parameters. When compared to the physical mixture, the CAMs of CRT:NRG 2:1 exhibited a 2.1-fold increase in CRT exposure (AUC 0- t ) and a 2.4-fold increase in plasma concentration ( C max ).

Polyphenols are natural compounds which are plant-based bioactive molecules, and have been the subject of growing interest in recent years. Characterized by multiple varieties, polyphenols are mostly found in fruits and vegetables. Currently, many diseases are waiting for a cure or a solution to reduce their symptoms. However, drug or other chemical strategies have limitations for using a treatment agent or still detection tool of many diseases, and thus researchers still need to investigate preventive or improving treatment. Therefore, it is of interest to elucidate polyphenols, their bioactivity effects, supplementation, and consumption. The disadvantage of polyphenols is that they have a limited bioavailability, although they have multiple beneficial outcomes with their bioactive roles. In this context, several different strategies have been developed to improve bioavailability, particularly liposomal and nanoparticles. As nutrition is one of the most important factors in improving health, the inclusion of plant-based molecules in the daily diet is significant and continues to be enthusiastically researched. Nutrition, which is important for individuals of all ages, is the key to the bioactivity of polyphenols.

"Horchata de chufa" is a beverage produced from tiger nut tubers, which yields a high amount of by-product. This study explored the functional properties of the Spanish tiger nut beverage (TNB) and its by-product (TNBP) together with the bioaccessibility and bioavailability of polyphenols in vitro . TNB and TNBP were characterized for polyphenols via LC/MS/MS and underwent in vitro digestion (INFOGEST). The total antioxidant capacity (TAC) of all bioaccessible fractions and digestion residues was assessed. Intestinal bioaccessible fractions were tested for the ability to inhibit the activity of digestive enzymes (α-amylase, α-glucosidase, and lipase) and the content of polyphenols, whose bioavailability was assessed in a Caco-2 cell model. Thirteen polyphenols were quantified and found to be more abundant in TNB (603 ± 1.4 μg g -1 DW) than in TNBP (187 ± 1.0 μg g -1 DW). Polyphenol bioaccessibility was higher for TNBP than that for TNB (57% vs. 27%), and despite a similar TAC of the intestinal bioaccessible fractions (10.2 ± 0.1 μmoL vs. 9.2 ± 0.03 μmoL eq. Trolox per g DW for TNB and TNBP, respectively), the different patterns of polyphenols released upon digestion suggested the higher ability of TNBP fraction to inhibit α-glucosidase and lipase. TNBP digestion residue showed higher TAC than TNB. Moreover, TNB polyphenols exhibited over 80% bioavailability, whereas TNBP polyphenols' bioavailability ranged from 62% to 84%. Overall, the findings demonstrated that TNBP maintains a high nutritional value, thus suggesting its possible reuse in innovative, healthy, and sustainable foods.

People are increasingly preparing milk tea using plant-based milks rather than cow's milk, e.g. , vegans, those with lactose intolerance, and those with flavor preferences. However, adding plant-based milks to tea may impact the digestion, release, and bioaccessibility of nutrients and nutraceuticals in both the tea and milk. In this study, oat milk tea model systems (OMTMSs) containing different fat and tea polyphenol concentrations were used to explore the impact of tea on macronutrient digestion in oat milk, as well as the impact of oat milk matrix on the polyphenol bioaccessibility in the tea. An in vitro gastrointestinal model that mimics the mouth, stomach, and small intestine was used. Tea polyphenols (>0.25%) significantly reduced the glucose and free fatty acids released from oat milk after intestinal digestion. Tea polyphenols (>0.10%) also inhibited protein digestion in oat milk during gastric digestion but not during intestinal digestion. The bioaccessibility of the polyphenols in the tea depended on the fat content of oat milk, being higher for medium-fat (3.0%) and high-fat (5.8%) oat milk than low-fat (1.5%) oat milk. Liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS/MS) analysis showed that lipids improved the tea polyphenol bioaccessibility by influencing the release of flavonoids and phenolic acids from the food matrices. These results provide important information about the impact of tea on the gastrointestinal fate of oat milk, and vice versa , which may be important for enhancing the healthiness of plant-based beverages.

Molecular modifications have been practiced for more than a century and nowadays they are widely applied in food, pharmaceutical, or other industries to manipulate the physicochemical, bioactivity, metabolic/catabolic, and pharmacokinetic properties. Among various structural modifications, the esterification/ O -acylation has been well-established in altering lipophilicity and bioactivity of parent bioactive compounds, especially natural polyphenolics, while maintaining their high biocompatibility. Meanwhile, various classic chemical and enzymatic protocols and other recently emerged cell factory technology are being employed as viable esterification strategies. In this contribution, the main motivations of phenolic esterification, including the tendency to replace synthetic alkyl phenolics with safer alternatives in the food industry to improve the bioavailability of phenolics as dietary supplements/pharmaceuticals, are discussed. In addition, the toxicity, metabolism, and commercial application of synthetic and natural phenolics are briefly introduced. Under these contexts, the mechanisms and reaction features of several most prevalent chemical and enzymatic esterification pathways are demonstrated. In addition, insights into the studies of esterification modification of natural phenolic compounds and specific pros/cons of various reaction systems with regard to their practical application are provided.

Green Tea polyphenols (GTP) are important bioactive compounds with excellent physiological regulation functions. However, they are easily destroyed by the gastric environment during digestion. In this work, a sodium alginate (SA)-gellan gum (GG) interpenetrating network (IPN) hydrogel was synthesized to protect and delivery GTP. The ratio of SA/GG significantly affects the network structure of IPN hydrogels and the performance of delivering GTP. The hydrogel formed by interpenetrating 20 % GG with 80 % SA as the main network had the highest water uptake (55 g/g), holding capacity (950 mg/g), and freeze-thaw stability, with springiness reaching 0.933 and hardness reaching 1300 g, which due to the filling effect and non-covalent interaction. Rheological tests showed that the crosslink density of IPN hydrogel in SA-dominated network was improved by the addition of GG to make it better bound to GTP, and the higher water uptake meant that the system could absorb more GTP-containing solution. This IPN hydrogel maintained 917.3 mg/g encapsulation efficiency at the highest loading capacity (1080 mg/g) in tests as delivery system. In in vitro digestion simulations, owing to the pH responsiveness, the IPN hydrogel reduced the loss of GTP in gastric fluid, achieving a bioaccessibility of 71.6 % in the intestinal tract., Competing Interests: Declaration of competing interest The authors declare that they have no know competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Yerba mate is increasingly acknowledged for its bioactive properties and is currently being incorporated into various food and pharmaceutical products. When roasted, yerba mate transforms into mate tea, consumed as a hot aqueous infusion, and has gained popularity. This study investigated the bioaccessibility of phenolic compounds, protein-polyphenol interactions, antioxidant activity, and bioactive peptides in roasted yerba mate infusions, utilizing whole, semi-skimmed, and skimmed bovine milk models. The phytochemical profile of roasted yerba mate was analyzed in infusions with water and milk (whole, semi-skimmed, and skimmed), before and after in vitro digestion, identifying 18 compounds that exhibited variations in composition and presence among the samples. Bioavailability varied across different milk matrices, with milk being four times more efficient as a solvent for extraction. Gastric digestion significantly impacted (p < 0.05) the release of phenolic compounds, such as chlorogenic acid and rutin, with only chlorogenic acid remaining 100 % bioavailable in the infusion prepared with skimmed milk. Protein-polyphenol interaction did not influence protein digestion in different infusions, as there was a similarity in the hydrolysis pattern during the digestive process. Changes in antioxidant activity during digestion phases, especially after intestinal digestion in milk infusions, were related to alterations in protein structures and digestive interactions. The evaluation of total phenolic compounds highlighted that skimmed milk infusion notably preserved these compounds during digestion. Peptidomic analysis identified 253, 221, and 191 potentially bioactive peptides for whole, semi-skimmed, and skimmed milk-digested infusions, respectively, with a focus on anti-inflammatory and anticancer activities, presenting a synergistic approach to promote health benefits. The selection of milk type is crucial for comprehending the effects of digestion and interactions in bioactive compound-rich foods, highlighting the advantages of consuming plant infusions prepared with milk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Grape pomace is the most important residual after wine making, and it is considered to be a very abundant source for the extraction of a wide range of polyphenols. These polyphenols exhibit a variety of bioactivities, such as antioxidant, anti-inflammatory, and anti-cancer. They are also beneficial in alleviating metabolic syndrome and regulating intestinal flora, etc. These health effects are most likely contributed by polyphenol metabolite, which are formed by the grape pomace phenolics after a complex metabolic process in vivo. Therefore, understanding the phenolic composition of grape pomace and its metabolism is the basis for an in-depth study of the biological activity of grape pomace polyphenols. In this paper, we first summarize the composition of phenolics in grape pomace, then review the recent studies on the metabolism of grape pomace phenolics, including changes in phenolics in the gastrointestinal tract, their pharmacokinetics in the systemic circulation, the tissue distribution of phenolic metabolites, and the beneficial effects of metabolites on intestinal health, and finally summarize the effects of human health status and dietary fiber on the metabolism of grape polyphenols. It is expected to provide help for the in-depth research on the metabolism and biological activity of grape pomace polyphenol extracts, and to provide theoretical support for the development and utilization of grape pomace.

Ethnopharmacological Relevance: Tsantan Sumtang (TS), a traditional Tibetan medicine, has been used in the clinic for the treatment of myocardial ischemia (MI) for ages, however, the bioactive ingredients that are responsible for improving MI remain unknown., Aim of the Study: This study investigated the chemical components of TS and their medicinal efficacies at cell levels, in order to expound the bioactive ingredients in TS., Materials and Methods: First, a response-surface methodology was employed to determine the optimum ethanol reflux extraction process of polyphenols in TS (PTS) due to their close correlation with MI improvement. Second, a serum pharmacochemistry technique was used to analyze the compounds of PTS absorbed into the blood of rats. Third, hypoxia-, H 2 O 2 -, and adriamycin (ADM)-induced H9c2 cell injury models were used to investigate the cardioprotective effects of these compounds in vitro. Fourth, protective effects of isovitexin, quercitrin, and isoeugenol on mitochondrial function were further tested., Results: The optimum extraction conditions for obtaining PTS were an ethanol concentration of 78.22%, an extraction time of 67.4 min, and a material-liquid ratio of 1:72.60 mL/g. Serum pharmacochemistry analysis detected 21 compounds, of which 11 compounds were always present in the blood within 5 h. Cytotoxicity and the protective effect of 11 compounds in hypoxia-, H 2 O 2 -, and ADM-induced H9c2 cell injury models shown that isovitexin, quercitrin, and isoeugenol had almost no cytotoxicity, and they could elevate the survival rate in injured H9c2 cells. Furthermore, isovitexin, quercitrin, and isoeugenol could decrease mitochondrial reactive oxygen species (ROS) releasion, inhibite mitochondrial permeability transition pore (mPTP) opening, ameliorate the change of mitochondrial membrane potential (MMP) to exert mitochondrial protection effect., Conclusion: Isovitexin, quercitrin, and isoeugenol exhibited cardioprotective effect at cell levles, these three compounds might be the bioactive ingredients in TS. These findings elucidate the pharmacodynamic substances and mechanisms of TS, guiding its clinical use., (Copyright © 2021. Published by Elsevier B.V.)

Aims: We investigated whether the consumption of Concord grape juice (CGJ) was associated with increased bioavailability of serum metabolites and their potential impact on cognitive performance in Veterans with Gulf War Illness (GWI)., Main Methods: Twenty-six veterans were selected from a cohort of 36 enrolled in a 24-week randomized, double-blind, Phase I/IIA clinical trial exploring whether the consumption of Concord grape juice (CGJ) was tolerable and safe in Veterans with GWI and improved cognitive function and fatigue. These 26 veterans were selected based on their completion of the entire 24-week protocol and documented adherence to the study beverage ≥80%. Differences in serum metabolite levels between CGJ and placebo at midpoint and endpoint were evaluated using two-way repeated measures ANOVA with post hoc Sidak's multiple comparison test. Bivariate correlations to assess for possible relationships between change in serum metabolite levels and change in cognitive function as measured by the Halstead Category Test-Russell Revised Version (RCAT) were also conducted., Key Findings: Seventy-six metabolites were identified and quantified in this study, with three (cyanidin-glucuronide, me-cyanidin-glucuronide, and me-malvidin-glucuronide) found to be significantly higher (p < 0.05) in the CGJ group compared to placebo at 24 weeks. Significant associations between changes in cognitive function and changes in serum levels of epicatechin-sulphate (r = 0.48, p = 0.01) and petunidin-glucuronide (r = 0.53, p < 0.01) from baseline to 24 weeks were also observed., Significance: Our data suggest that dietary supplementation with CGJ is associated with increased bioavailability of specific phenolic metabolites, some of which may be correlated with cognitive performance., (Copyright © 2021. Published by Elsevier Inc.)

Fifty (50) phytocompounds from several subclasses of polyphenols, chosen based on their abundance in the plant world, were analyzed through density functional methods, using computational tools to evaluate their oral availability and particular bioactivity on several cell modulators; key descriptors and molecular features related to the electron density and electrostatic potential for the lowest energy conformers of the investigated molecules were computed. An analysis of the bioactivity scores towards six cell modulators (GPCR ligand, ion channel modulator, kinase inhibitor, nuclear receptor ligand, protease inhibitor and enzyme inhibitor) was also achieved, in the context of investigating their potential side effects on the human digestive processes. Summarizing, computational results confirmed in vivo and in vitro data regarding the high bioavailability of soy isoflavones and better bioavailability of free aglycones in comparison with their esterified and glycosylated forms. However, by a computational approach analyzing Lipinski's rule, apigenin and apigenin-7- O -rhamnoside, naringenin, hesperetin, genistein, daidzin, biochanin A and formonetin in the flavonoid series and all hydroxycinnamic acids and all hydroxybenzoic acids excepting ellagic acid were proved to have the best bioavailability data; rhamnoside derivatives, the predominant glycosides in green plants, which were reported to have the lowest bioavailability values by in vivo studies, were revealed to have the best bioavailability data among the studied flavonoids in the computational approach. Results of in silico screening on the phenolic derivatives series also revealed their real inhibitory potency on the six parameters studied, showing a remarkable similitude between the flavonoid series, while flavonoids were more powerful natural cell modulators than the phenyl carboxylic acids tested. Thus, it can be concluded that there is a need for supplementation with digestive enzymes, mainly in the case of individuals with low digestive efficiency, to obtain the best health benefits of polyphenols in humans.

Background: Increasing nitric oxide bioavailability may induce physiological effects that enhance endurance exercise performance. This review sought to evaluate the performance effects of consuming foods containing compounds that may promote nitric oxide bioavailability., Methods: Scopus, Web of Science, Ovid Medline, EMBASE and SportDiscus were searched, with included studies assessing endurance performance following consumption of foods containing nitrate, L-arginine, L-citrulline or polyphenols. Random effects meta-analysis was conducted, with subgroup analyses performed based on food sources, sex, fitness, performance test type and supplementation protocol (e.g. duration)., Results: One hundred and eighteen studies were included in the meta-analysis, which encompassed 59 polyphenol studies, 56 nitrate studies and three L-citrulline studies. No effect on exercise performance following consumption of foods rich in L-citrulline was identified (SMD=-0.03, p=0.24). Trivial but significant benefits were demonstrated for consumption of nitrate and polyphenol-rich foods (SMD=0.15 and 0.17, respectively, p<0.001), including performance in time-trial, time-to-exhaustion and intermittent-type tests, and following both acute and multiple-day supplementation, but no effect of nitrate or polyphenol consumption was found in females. Among nitrate-rich foods, beneficial effects were seen for beetroot, but not red spinach or Swiss chard and rhubarb. For polyphenol-rich foods, benefits were found for grape, (nitrate-depleted) beetroot, French maritime pine, Montmorency cherry and pomegranate, while no significant effects were evident for New Zealand blackcurrant, cocoa, ginseng, green tea or raisins. Considerable heterogeneity between polyphenol studies may reflect food-specific effects or differences in study designs and subject characteristics. Well-trained males (V̇O 2max ≥65 ml.kg.min -1 ) exhibited small, significant benefits following polyphenol, but not nitrate consumption., Conclusion: Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent. Highly trained endurance athletes do not appear to benefit from consuming nitrate-rich foods but may benefit from polyphenol consumption. Further research into food sources, dosage and supplementation duration to optimise the ergogenic response to polyphenol consumption is warranted. Further studies should evaluate whether differential sex-based responses to nitrate and polyphenol consumption are attributable to physiological differences or sample size limitations., Other: The review protocol was registered on the Open Science Framework ( https://osf.io/u7nsj ) and no funding was provided., (© 2021. The Author(s).)

The present review summarizes the studies carried out on this topic in the last five years. According to the new definitions, among all the compounds included in the group of prebiotics, polyphenols are probably the most important secondary metabolites produced by the plant kingdom. Many of these types of polyphenols have low bioavailability, therefore reaching the colon in unaltered form. Once in the colon, these compounds interact with the intestinal microbes bidirectionally by modulating them and, consequently, releasing metabolites. Despite much research on various metabolites, little is known about the chemistry of the metabolic routes used by different bacteria species. In this context, this review aims to investigate the prebiotic effect of polyphenols in preclinical and clinical studies, highlighting that the consumption of polyphenols leads to an increase in beneficial bacteria, as well as an increase in the production of valuable metabolites. In conclusion, there is much evidence in preclinical studies supporting the prebiotic effect of polyphenols, but further clinical studies are needed to investigate this effect in humans.

Functional properties and biological activities of plant-derived polyphenolic compounds have gained great interest due to their epidemiologically proven health benefits and diverse industrial applications in the food and pharmaceutical industry. Moreover, the food processing conditions and certain chemical reactions such as pigmentation, acylation, hydroxylation, and glycosylation can also cause alteration in the stability, antioxidant activity, and structural characteristics of the polyphenolic compounds. Since the (poly)phenols are highly reactive, to overcome these problems, the formulation of a complex of polyphenolic compounds with natural biopolymers is an effective approach. Besides, to increase the bioavailability and bioaccessibility of polyphenolic compounds, milk proteins such as whey protein concentrate, sodium caseinate, and milk protein concentrate act as natural vehicles, due to their specific structural and functional properties with high nutritional value. Therefore, milk proteins are suitable for the delivery of polyphenols to parts of the gastrointestinal tract. Therefore, this review reports on types of (poly)phenols, methods for the analysis of binding interactions between (poly)phenols-milk proteins, and structural changes that occur during the interaction.

Ferritin, a protein with an 8-nm cage structure, can encapsulate and deliver bioactive molecules. In this study, succinylation was adopted to modify plant ferritin to fabricate succinylated red been ferritin (SRBF) at pH 8.0. The SRBF was retained as a cage-like shape (12 nm diameter), while its secondary structure was altered, rendering higher negative charge accompanies by decreased surface hydrophobicity. The SRBF also demonstrated favorable property of reversible assembly regulated by pH-transitions (pH 2.0/7.0), thus enabled successful encapsulation of epigallocatechin gallate (EGCG) for fabrication of EGCG-loaded SRBF complexes with a diameter of ~12 nm. Succinylation enhanced the thermal stabilities of ferritin and the embedded EGCG. Moreover, SRBF markedly improved the transport efficiency of EGCG in Caco-2 monolayers relative to EGCG and that encapsulated in unmodified ferritin. These findings have extended the succinylation reaction for the cage-like protein modification, and facilitated the usage of ferritin variant in delivery of bioactive molecules., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Plant-based polyphenols are natural compounds, present in fruits and vegetables. During recent years, polyphenols have gained special attention due to their nutraceutical and pharmacological activities for the prevention and treatment of human diseases. Nevertheless, their photosensitivity and low bioavailability, rapid metabolism and short biological half-life represent the major limitations for their use, which could be overcome by polyphenols encapsulation (flavonoids and non-flavonoids) into chitosan (CS)-tripolyphosphate (TPP) based nanoparticles (NP). In this review, we particularly focused on the ionic gelation method for the NP design. This contribution exhaustively discusses and compares results of scientific reports published in the last decade referring to ionic gelation applied for the protection, controlled and site-directed delivery of polyphenols. As a consequence, CS-TPP NP would constitute true platforms to transport polyphenols, or a combination of them, to be used for the designing of a new generation of drugs or nutraceuticals., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.

Chronodisruption leads to obesity and other metabolic disorders that can be alleviated by food-derived potential chronobiotics, such as phytomelatonin (PMT), phenolic compounds (PCs) and dietary fiber rich pistachios. Pistachios with (PN + SC) or without (PN) the seed coat were investigated for their in vitro chronobiotic potential since they are one of the main reported PMT sources. Consequently we evaluated the bioaccessibility, permeability, and biosynthesis of pistachio chronobiotics, particularly PMT, during gastrointestinal and colonic fermentation. The maximum in vitro bioaccessibility and apparent permeability (efflux-prone) of PCs, flavonoids and PMT were sample-specific [∼1.3% (both), 27 and 3.4% (PN + SC)], but additional amounts (flavonoids > PCs > PMT) were released under simulated colonic conditions. Short-chain fatty acids (SCFAs; 38 mM; >50% butyrate, PN + SC > PN) and some metabolites (e.g., indole, benzaldehyde, phenolic acids, and aliphatic/aromatic hydrocarbons) were detected depending on the sample. The predominant pistachio butyrate production during in vitro colonic fermentation can improve chronodisruption and benefit obese individuals. Pistachio's digestion increases the bioaccessibility and intestinal permeability of potential chronobiotics (PMT and PCs) and the biosynthesis of colonic metabolites (SCFAs, among others) also with chronobiotic potential.

Scope: Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated., Methods and Results: Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L -1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L -1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity., Conclusion: Curcuminoids could be coadjuvants that might help fight BC upon regular consumption., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Background: Oxidative stress and inflammation contribute to the etiopathogenesis of several human chronic diseases, such as cancer, diabetes, cardiovascular diseases and metabolic syndrome. Besides classic stimuli, such as reactive oxidant species, endotoxins (i.e., bacteria lipopolysaccharide), cytokines or carcinogens, oxidative stress and inflammation can be triggered by a poor diet and an excess of body fat and energy intake. Strawberry and honey are common rich sources of nutrients and bioactive compounds, widely studied for their roles exerted in health maintenance and disease prevention., Purpose: This review aims to summarize and update the effects of strawberry and honey against oxidative stress and inflammation, with emphasis on metabolism and on the main molecular mechanisms involved in these effects., Methods: A wide range of literature, published in the last 10 years, elucidating the effects of strawberry and honey in preventing oxidative stress and inflammation both in vitro (whole matrix and digested fractions) and in vivo was collected from online electronic databases (PubMed, Scopus and Web of Science) and reviewed., Results: Strawberry and honey polyphenols may potentially prevent the chronic diseases related to oxidative stress and inflammation. Several in vitro and in vivo studies reported the effects of these foods in suppressing the oxidative stress, by decreasing ROS production and oxidative biomarkers, restoring the antioxidant enzyme activities, ameliorating the mitochondrial antioxidant status and functionality, among others, and the inflammatory process, by modulating the mediators of acute and chronic inflammation essential for the onset of several human diseases. These beneficial properties are mediated in part through their ability to target multiple signaling pathways, such as p38 MAPK, AMPK, PI3K/Akt, NF-κB and Nrf2., Conclusions: Available scientific literature show that strawberry and honey may be effective in preventing oxidative stress and inflammation. The deep evaluation of the factors that affect their metabolism as well as the assessment of the main molecular mechanisms involved are of extreme importance for the possible therapeutic and preventive benefit against the most common human diseases. However, published literature is still scarce so that deeper studies should be performed in order to evaluate the bioavailability of these food matrices and their effects after digestion., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.

Dietary plant polyphenols are natural bioactive compounds that are increasingly attracting the attention of food scientists and nutritionists because of their nutraceutical properties. In fact, many studies have shown that polyphenol-rich diets have protective effects against most chronic diseases. However, these health benefits are strongly related to both polyphenol content and bioavailability, which in turn depend on their origin, food matrix, processing, digestion, and cellular metabolism. Although most fruits and vegetables are valuable sources of polyphenols, they are not usually consumed raw. Instead, they go through some processing steps, either industrially or domestically (e.g., cooling, heating, drying, fermentation, etc.), that affect their content, bioaccessibility, and bioavailability. This review summarizes the status of knowledge on the possible (positive or negative) effects of commonly used food-processing techniques on phenolic compound content and bioavailability in fruits and vegetables. These effects depend on the plant type and applied processing parameters (type, duration, media, and intensity). This review attempts to shed light on the importance of more comprehensive dietary guidelines that consider the recommendations of processing parameters to take full advantage of phenolic compounds toward healthier foods.

Lipophilic polyphenol compounds (LPCs) are claimed to exhibit a broad spectrum of biological activities that may improve human health and wellbeing, including antioxidant, anti-inflammatory, and anti-cancer properties. Nanoemulsion-based delivery systems have been developed to encapsulate LPCs so as to increase their food matrix compatibility, physicochemical stability, and bioavailability. LPCs vary in their structural features, including the number and position of phenolic hydroxyl, ketone, and aliphatic groups, which results in different molecular, physicochemical, and gastrointestinal properties. In this study, we examined the impact of plant-based carrier oils (coconut, sunflower, and flaxseed oils) and LPC type (curcumin, resveratrol, and quercetin) on the in vitro gastrointestinal fate of polyphenols loaded into quillaja saponin-stabilized nanoemulsions. Coconut oil contains high levels of medium-chain saturated fatty acids (MC-SFAs), sunflower oil contains high levels of long-chain monounsaturated fatty acids (LC-MUFAs), and flaxseed oil contains high levels of long-chain polyunsaturated fatty acids (LC-PUFAs). The encapsulation efficiency and gastrointestinal stability of the LPCs were slightly lower in the MC than the LC oils. Differences in the gastrointestinal stability of the three LPCs were linked to differences in their oil-water partition coefficients. Some of the LPCs inhibited lipid digestion for certain oil types. In particular, resveratrol retarded the digestion of all three oils, but it still had the highest GIT stability and bioaccessibility. This study provides valuable information about the gastrointestinal fate of LPC-loaded nanoemulsions and highlights important differences in the behavior of LPCs with different characteristics. This knowledge may facilitate the design of more effective plant-based delivery systems for bioactive lipophilic polyphenols.

Agrofood coproducts are used to enrich meat products to reduce harmful compounds and contribute to fiber and polyphenol enrichment. Pork liver pâtés with added persimmon coproducts (3 and 6%; PR-3 and PR-6, respectively) were developed. Therefore, the aim was to study the effect of their in vitro gastrointestinal digestion on: the free and bound polyphenol profile (HPLC) and their colon-available index; the lipid oxidation (TBARs); and the stability of the fatty acid profile (GC). Furthermore, the effect of lipolysis was investigated using two pancreatins with different lipase activity. Forty-two polyphenols were detected in persimmon flour, which were revealed as a good source of bound polyphenols in pâtés, especially gallic acid (164.3 µg/g d.w. in PR-3 and 631.8 µg/g d.w. in PR-6). After gastrointestinal digestion, the colon-available index in enriched pâté ranged from 88.73 to 195.78%. The different lipase activity in the intestinal phase caused significant differences in bound polyphenols' stability, contributing to increased lipid oxidation. The fatty acids profile in pâté samples was stable, and surprisingly their PUFA content was raised. In conclusion, rich fatty foods, such as pâté, are excellent vehicles to preserve bound polyphenols, which can reach the colon intact and be metabolized by the intestinal microbiome.

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood-brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut-microbiota-brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer's disease.

Consuming polyphenol-rich fruits and vegetables, including blueberries, is associated with beneficial health outcomes. Interest in enhancing polyphenol intakes via dietary supplements has grown, though differences in fruit versus supplement matrix on gut microbiota and ultimate phenolic metabolism to bioactive metabolites are unknown. To evaluate this, 5-month-old, ovariectomized, Sprague-Dawley rats were gavaged for 90 d with a purified extract of blueberry polyphenols (0, 50, 250, or 1000 mg total polyphenols per kg bw per d) or lyophilized blueberries (50 mg total polyphenols per kg bw per d, equivalent to 150 g fresh blueberries per day in humans). Urine, feces, and tissues were assessed for gut microbiota and phenolic metabolism. Significant dose- and food matrix-dependent effects were observed at all endpoints measured. Gut microbial populations showed increased diversity at moderate doses but decreased diversity at high doses. Urinary phenolic metabolites were primarily observed as microbially derived metabolites and underwent extensive host xenobiotic phase II metabolism. Thus, blueberry polyphenols in fruit and supplements induce differences in gut microbial communities and phenolic metabolism, which may alter intended health effects.

The aim of this study was to evaluate the bioaccessibility of (poly)phenolic compounds in Tudela artichokes (Cynara scolymus cv. Blanca de Tudela) after an in vitro gastrointestinal digestion and the effect of the human colonic microbiota. A total of 28 (poly)phenolic compounds were identified and quantified by LC-MS/MS in raw, boiled, sous vide and microwaved Tudela artichokes. Out of these, sixteen were phenolic acids, specifically caffeoylquinic acids (CQAs) and other minor hydroxycinnamic acid derivatives, ten flavonoids belonging to the family of flavones (apigenin and luteolin derivatives) and two lignans (pinoresinol derivatives). Sous vide and microwaving caused mainly transesterification reactions of CQAs but maintained or even augmented the total (poly)phenolic contents of artichokes, while boiling decreased (poly)phenolic compounds by 25% due to leaching into the boiling water. Heat treatment exerted a positive effect on the bioaccessibility of (poly)phenols after gastrointestinal digestion. In raw artichokes, only 1.6% of the total (poly)phenolic compounds remained bioaccessible after gastrointestinal digestion, while in artichoke samples cooked by sous vide, boiled and microwaved, the percentage of bioaccessibility was 60.38%, 59.93% and 39,03% respectively. After fecal fermentation, 20 native (poly)phenolic compounds and 11 newly formed catabolites were quantified. 48 h of fecal fermentation showed that native (poly)phenols are readily degraded by colonic microbiota during the first 2 h of incubation. The colonic degradation of artichoke (poly)phenols follows a major pathway that involves the formation of caffeic acid, dihydrocaffeic acid, 3-(3'-hydroxyphenyl)propionic acid, 3-phenylpropionic acid and phenylacetic acid, with 3-phenylpropionic acid being the most abundant end product. The catabolic pathways for colonic microbial degradation of artichoke CQAs are proposed.

Recently the Salvia Miltiorrhiza-Moutan Cortex (SM-MC) herb pair is considered as a promising Chinese medicinal mixture exhibiting a range of pharmacological activities, including treating cardiovascular disease due to its unique composition. In this study, we conducted the comparative pharmacokinetic analysis of seven main bioactive components of SM-MC in a different model rat. A straightforward ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) strategy that could simultaneously evaluate the levels of seven compounds was used to ensure the reliability of these pharmacokinetic analyses in rat plasma. The rat plasma samples were collected from normal, sham-operated, and myocardial ischemia-reperfusion injury (MIRI) groups at predetermined time points after the administration of SM-MC. The main pharmacokinetic parameters were detected and calculated. We successfully assessed the maximum concentration (C max ), time to C max (T max ), the elimination rate constant (λ z ), total half-life (t 1/2 ), total body clearance (CL), and the area under the concentration-time curve from 0 to last sampling time (AUC 0-t ) and extrapolated to infinity (AUC 0-∞ ). To sum up, an optimized UPLC-MS/MS approach that could be used to rapidly, simultaneously, and sensitively detect seven bioactive compounds derived from SM-MC extract preparations was successfully developed, which may offer a pharmacokinetic basis for preclinical and clinical studies of SM-MC herb pair for treating MIRI., (© 2020 John Wiley & Sons, Ltd.)

The purposes of this study were to explore the preventive and treatment effects of Hunan insect tea polyphenols (HITPs) on gastric injury in mice induced by HCl/ethanol and to investigate their molecular mechanisms of action. Both HITPs and ranitidine inhibited the formation and further deterioration of gastric mucosal lesions, reduced the secretion of gastric juice, and raised gastric juice pH compared to the control. The HITPs-H treated group had lower serum levels of motilin, substance P, and endothelin than the control group, but they had higher serum levels of vasoactive intestinal peptide and somatostatin. Mice treated with HITPs had lower serum levels of cytokines interleukin (IL)-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ than the control group. The activities of superoxide dismutase (SOD), nitric oxide, and glutathione peroxidase (GSH-Px) were higher in the gastric tissues of HITP-treated mice, but the malondialdehyde content was lower. Quantitative PCR analysis indicated that the mRNA expression of occludin, epidermal growth factor (EGF), EGF receptor (EGFR), vascular EGF (VEGF), inhibitor kappaB-α, cuprozinc-superoxide dismutase, manganese-superoxide dismutase, GSH-Px, neuronal nitric oxide synthase, and endothelial NOS increased significantly in the gastric tissues of HITP-treated mice. However, the activated B cell, inducible NOS, cyclooxygenase-2, TNF-α, IL-1 beta, and IL-6 mRNA expression levels in the HITPs group were lower than those in the control group. The protective effect of a high concentration (200 mg per kg bw) of HITPs on gastric injury induced by HCl/ethanol was stronger than that of a low concentration (100 mg per kg bw) of HITPs. High-performance liquid chromatography (HPLC) revealed that the HITPs contained cryptochlorogenic acid, (-)-epicatechin gallate, and isochlorogenic acid C. Taken together, our findings indicate that the HITPs played a role in the prevention of gastric damage. The antioxidant effect of the HITPs contributed to their potential value in the prevention and treatment of gastric injury. HITPs have broad prospects as biologically active substances for food development.

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.

To compare the encapsulation of annatto extract by external gelation (EG) and internal gelation (IG) and to maximize process yield (% Y), two central composite designs were proposed. Calcium chloride (CaCl 2 ) concentration (0.3-3.5%), alginate to gelling solution ratio (1:2-1:6); acetic acid (CH 3 COOH) concentration (0.2-5.0%) and alginate to gelling solution ratio (1:2-1:6) were taken as independent variables for EG and IG respectively. Release studies were conducted under different conditions; morphology, particle size, the encapsulation efficiency (EE), and release mechanism were evaluated under optimized conditions. The optimized EG conditions were 0.3% CaCl 2 and 1:1.2 alginate to gelling solution ratio, whereas a 0.3% CH 3 COOH and 1:5 alginate to gelling solution ratio were optimized conditions for IG. When 20% extract was employed, the highest EE was achieved, and the largest release was obtained at a pH 6.5 buffer. The Peppas-Sahlin model presented the best fit to experimental data. Polyphenol release was driven by diffusion, whereas bixin showed anomalous release. These results are promising for application as modulated release agents in food matrices.

Inflammation is the main key role in developing chronic diseases including cancer, cardiovascular diseases, diabetes, arthritis, and neurodegenerative diseases which possess a huge challenge for treatment. With massively compelling evidence of the role played by nutritional modulation in preventing inflammation-related diseases, there is a growing interest into the search for natural functional foods with therapeutic and preventive actions. Honey, a nutritional healthy product, is produced mainly by two types of bees: honeybee and stingless bee. Since both types of honey possess distinctive phenolic and flavonoid compounds, there is recently an intensive interest in their biological and clinical actions against inflammation-mediated chronic diseases. This review shed the light specifically on the bioavailability and bioaccessibility of honey polyphenols and highlight their roles in targeting inflammatory pathways in gastrointestinal tract disorders, edema, cancer, metabolic and cardiovascular diseases and gut microbiota.

Aims: This is a pharmacokinetic study of Salviae miltiorrhizae and ligustrazine hydrochloride injection. The study aimed to evaluate the mechanism of action, safety and rational clinical use of Salviae miltiorrhizae and ligustrazine hydrochloride injection., Background: Salviae miltiorrhizae and ligustrazine hydrochloride injection is a compound preparation consisted of Salvia miltiorrhiza extract and ligustrazine hydrochloride for the treatment of cardiovascular and cerebrovascular diseases in China., Objective: The study aimed to develop a rapid and sensitive high-performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS) method for simultaneous determination of six major active ingredients of Salviae miltiorrhizae and ligustrazine hydrochloride injection, namely danshensu, protocatechuic aldehyde, rosmarinic acid, lithospermic acid, salvianolic acid A, and ligustrazine hydrochloride, in rat plasma., Methods: Plasma samples were precipitated with methanol, which was spiked with ascorbic acid and the supernatant was separated on a Waters Cortecs C18 column, by using a gradient mobile phase system of acetonitrile-water containing 0.05% formic acid (v/v). For internal standards, puerarin was selected for the five salvianolic acids, while isofraxidin was used for ligustrazine hydrochloride. Besides, electrospray ionization in negative mode and multiplereaction monitoring were used to identify and quantify the five salvianolic acids, whereas ligustrazine hydrochloride was quantified at 310 nm using the diode array detector., Results: Noticeably, all calibration curves showed good linearity (R2>0.99) over the concentration range, with a lower limit of quantification between 0.00411 and 0.0369 μg/mL for salvianolic acids, and 1.74 μg/mL for ligustrazine hydrochloride. Next, the precision of the developed method was evaluated by intra- and inter-day assays, and the percentage of relative standard deviation was within 10%. Although the extraction efficiency of some salvianolic acids was not very satisfactory, the sensitivity of the analytical method met the analysis requirements of rat plasma samples. Moreover, the validated method was successfully applied to a pharmacokinetic study of Salviae miltiorrhizae and ligustrazine hydrochloride injection in the rat model., Conclusion: Linear pharmacokinetic characteristics were observed for the six active ingredients after intravenous infusion administration in rats within the dose range examined here. In summary, our study proposed a HPLC-DADMS/ MS method with the simultaneous determination of multiple ingredients, and demonstrated its applicability in pharmacokinetic studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Scope: More than a decade ago, the concept of "metabolic endotoxemia" is elaborated on the fact that some bacterial components, classified as microbial associated membrane pathogens (MAMPs) can pass through the gut barrier and create a systemic low tone inflammation., Methods and Results: The translocation of lipopolysaccharides and its contribution to systemic inflammation are largely studied in murine models of obesity, allowing to unravel the molecular pathways involved in the process. Many different pathological contexts evoke the loss of gut barrier as an event contributing to inflammation and thereby driving metabolic and behavioral alterations., Conclusion: This review describes the role of nutrition as a modulator of metabolic regulation and focuses on the contribution of the gut microbiota in the process of the production of a large diversity of bioactive metabolites. The two first sections of the review will be dedicated to the impact of nutritional disorders on both the gut microbiota composition and on metabolic inflammation. The last and more prominent section will describe the role of different nutrient-derived gut metabolites on the gut barrier integrity, metabolic inflammation, and peripheral tissue alterations during obesity or associated complications., (© 2020 Wiley-VCH GmbH.)

Background: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles., Objectives: The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model., Methods: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel., Results: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 μg/ml*h (p<0.05), 26.01 ±0.90 μg/ml*h (p>0.05) and 32.80 ±2.51 μg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 μg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 μg/ml versus 6.12 ±0.21 μg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05)., Conclusion: The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Flavonoids are known to undergo phase II metabolism and produce metabolites with similar or stronger biological effects compared to the parent flavonoids. However, the limited cellular uptake and bioavailability restrict their clinical use. We synthesized phloridzin docosahexaenoate (PZ-DHA), a novel fatty acid ester of polyphenol, through an acylation reaction with the aim of increasing the cellular availability and stability of the parent biomolecules, phloridzin (PZ) and docosahexaenoic acid (DHA). Here, we report metabolites and pharmacokinetic parameters of PZ-DHA, determined using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. PZ-DHA was taken-up by human (MDA-MB-231, MDA-MB-468, and MCF-7) and mouse (4T1) mammary carcinoma and human non-malignant mammary epithelial cells (MCF-10A) in cellular uptake assays. Our results suggested that the acylation improves the cellular uptake of PZ and stability of DHA within cells. In mouse hepatic microsomal assays, two major glucuronides of PZ-DHA, PZ-DHA-4-O-glucuronide and PZ-DHA-4'-O-glucuronide (MW = 923.02 g/mol), were detected. One tri-methylated- (4,4',6'-O-trimethyl-PZ-DHA) (MW = 788.88 g/mol) and one di-sulphated- (PZ-DHA-4,4'-O-disulphide) PZ-DHA metabolite (MW = 906.20 g/mol) were also identified. Intraperitoneal injections of PZ-DHA (100 mg/kg) into Balb/c female mice was rapidly absorbed with a serum C max and T max of 23.7 µM and 60 min, respectively, and rapidly eliminated (t 1/2  = 28.7 min). PZ-DHA and its metabolites are readily distributed throughout the body (V d  = 57 mL) into many organs. We identified in vitro and in vivo metabolites of PZ-DHA, which could be tested for potential use to treat diseases such as cancer in multiple organ systems.

The consumption of orange juice provides high concentrations of health-promoting bioactive compounds, the amount of which may increase upon alcoholic fermentation. Although fermentation may offer new prospects for the industry of orange-related products, there is a lack of studies reporting the influence of controlled alcoholic fermentation on the bioavailability of orange juice (poly)phenols in humans. The aim of this study was to evaluate the absorption profile, pharmacokinetic parameters, and urinary excretion of orange juice (poly)phenols in nine volunteers after acute administration of an orange juice and a beverage prepared after controlled alcoholic fermentation of the juice. Plasma and urine samples were analysed through a UHPLC-ESI-MS/MS targeted approach. A total of 24 (poly)phenol metabolites including both flavanone and phenolic acid derivatives were quantified, most of them being recorded only in urine. Phase II conjugates of hesperetin and naringenin were the main metabolites in plasma, while phenolic acids, in particular hydroxybenzoic acids, were the main compounds in urine. (Poly)phenols in both beverages were highly bioavailable (between 46 and 59%) and a notable inter-individual variability was seen. Significant treatment × time interactions were recorded for the sum of flavanones and phenolic acids in plasma, the (poly)phenols in the fermented juice being absorbed faster than after orange juice intake. Nevertheless, despite the food matrix having an impact on the absorption profile of orange juice (poly)phenols, this did not influence the pharmacokinetic parameters and urinary excretion of the (poly)phenol metabolites., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Stability of protein-polyphenol aggregate particles, created by complexing polyphenols from blueberry and muscadine grape pomaces with a rice-pea protein isolate blend, was evaluated in an in vitro gastrointestinal model. Recovery index (RI; % total phenolics present post-digestion) was 69% and 62% from blueberry and muscadine grape protein-polyphenol particles, compared to 23% and 31% for the respective pomace extracts. Anthocyanins RI was 52% and 42% from particles (6% and 13% from pomace extracts), and proanthocyanidins RI was 77% and 73% from particles (25% and 14% from pomace extracts), from blueberry and grape, respectively. Protein-polyphenol particle digests retained 1.5 to 2-fold higher antioxidant capacity and suppressed the expression of pro-inflammatory cytokines, iNOS, IL6, and IL1β, compared to unmodified extract digests, which only suppressed IL6. Protein-polyphenol particles as a delivery vehicle in foods may confer better stability during gastrointestinal transit, allow protected polyphenols to reach the gut microbiota, and preserve polyphenol bioactivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects ( n = 13, BMI = 22.7 ± 0.4 kg/m 2 ) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (C max ) of gallotannin metabolites were significantly increased ( p < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the C max of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake ( p < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.

In order to improve the bioavailability of Juglans regia L. polyphenols (JRP) in human body, the novel Juglans regia L. polyphenols-Hohenbuehelia serotina polysaccharides (HSP) nanoparticles (JRP-HSP NPs) were synthesized based on electrostatic interaction. Moreover, the physicochemical properties, morphologies and gastrointestinal digestive characteristics of JRP-HSP NPs were respectively measured and analyzed. Among four kinds of JRP-HSP NPs prepared by different condition of mass ratio, JRP-HSP NPs (1:16) with encapsulation efficiency of 51.62%, average particle size of 341.0 nm, and zeta potential of -29.3 mv, presented better physicochemical properties, such as thermal stability, photostability and crystalline properties. Morphological analysis revealed JRP-HSP NPs (1:16) appeared spherical and almost uniform. Through evaluation of simulated gastrointestinal digestion, JRP-HSP NPs prevented the variation of phenolic composition induced by gastrointestinal digestion, which was similar as the one of undigested JRP, while un-encapsulated JRP exhibited totally different state due to degradation and biotransformation, suggesting that JRP-HSP NPs possessed the sustained release characteristics in gastrointestinal system. This study provided a non-toxic strategy to encapsulate polyphenols for improving their bioavailability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Polyphenols have demonstrated several potential biological activities, notably antitumoral activity dependent on immune function. In the present review, we describe studies that investigated antitumor immune responses influenced by polyphenols and the mechanisms by which polyphenols improve the immune response. We also discuss the limitations in related areas, especially unexplored areas of research, and next steps required to develop a therapeutic approach utilizing polyphenols in oncology., (Copyright © 2020. Published by Elsevier Inc.)

Olive (Olea europaea L.) leaves and tea (Camellia sinensis) are rich sources of bioactive compounds, especially polyphenols. Our previous studies have evidenced the potential use of Saccharomyces cerevisiae as a natural delivery system for these antioxidants and a means to improve their bioaccessibility in the human gut. In the present work, the antiproliferative effect of green tea (GT), black tea (BT) and olive leaves (OL) infusions and suspensions of S. cerevisiae were evaluated, for the first time, in human colon cancer cells (Caco-2) after biosorption and in vitro gastrointestinal digestion. The bioaccessible fractions (BF) were not overtly cytotoxic, not affecting cell viability. ROS and mitochondrial membrane potential changes (Δψm) values were reduced compared with control cells. Moreover, all the BF after biosorption induced a significant (p < 0.05) increase in cell proportions in S-phase. The arrest of the cell cycle was reversible without induction of apoptosis, suggesting that the biosorbed phenolics in both infusions and suspensions act as cytostatic agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The prevalence of obesity has steadily increased worldwide over the past three decades. The conventional approaches to prevent or treat this syndrome and its associated complications include a balanced diet, an increase energy expenditure, and lifestyle modification. Multiple pharmacological and non-pharmacological interventions have been developed with the aim of improving obesity complications. Recently, the use of functional foods and their bioactive components is considered a new approach in the prevention and management of this disease. Due to their biological properties, polyphenols may be considered as nutraceuticals and food supplement recommended for different syndromes. Polyphenols are a class of naturally-occurring phytochemicals, some of which have been shown to modulate physiological and molecular pathways involved in energy metabolism. Polyphenols could act in the stimulation of β-oxidation, adipocyte differentiation inhibition, counteract oxidative stress, etc. In this narrative review, we considered the association between polyphenols (resveratrol, quercetin, curcumin, and some polyphenolic extracts) and obesity, focusing on human trials. The health effects of polyphenols depend on the amount consumed and their bioavailability. Some results are contrasting, probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), and chemical forms of the dietary polyphenols used. But, in conclusion, the data so far obtained encourage the setting of new trials, necessary to validate benefic role of polyphenols in obese individuals.

Emerging evidence from human intervention trials indicates health benefits of consuming blackcurrant fruit, including improvements to cognitive performance, modulation of blood flow, regulation of blood glucose and inhibition of enzymes underpinning normal cognitive function. Of particular relevance is our previous demonstration of monoamine oxidase (MAO)-A and B inhibition after the consumption of a New Zealand "Blackadder" blackcurrant juice in humans. The current study uses a double-blind, placebo-controlled, randomised cross- over design to assess the pharmacodynamics of the effects on platelet MAO-B inhibition and associated substrates, plasma prolactin levels and blood glucose levels after consumption of a single serve of "Blackadder" blackcurrant juice standardised to 500 mg polyphenols. Eight healthy male (20--35 years) participants completed the trial. Measurements were obtained at baseline 15, 30, 45, 60, 100, 120, 150, 180, 240 mins and 24 h post dose. A fast, absolute and reversible inhibition of blood platelet MAO-B ( P  < 0.001) and a significant but delayed reduction in plasma prolactin ( P  < 0.001) were observed following the consumption of "Blackadder" blackcurrant juice when compared to a placebo control. No interpretable changes in substrates of MAO or associated metabolites were seen. These data provide a clear time course of the reversible inhibition of MAO-B after the single consumption of a of New Zealand "Blackadder" blackcurrant juice standardised at 500 mg of polyphenols and, therefore, provide a therapeutic window on which to base future nutritional interventions.